Mutations at the M2 and M3 Transmembrane Helices of the GABARs α and β Subunits Affect Primarily Late Gating Transitions Including Opening/Closing and Desensitization.

GABA type A receptors (GABARs) belong to the pentameric ligand-gated ion channel (pLGIC) family and play a crucial role in mediating inhibition in the adult mammalian brain. Recently, a major progress in determining the static structure of GABARs was achieved, although precise molecular scenarios underlying conformational transitions remain unclear. The ligand binding sites (LBSs) are located at the extracellular domain (ECD), very distant from the receptor gate at the channel pore.